磁热响应复合载药胶束的热化疗协同效应

以N-异丙基丙烯酰胺(NIPAM)、N,N-二甲基丙烯酰胺(DMAM)为单体,通过可逆加成-断裂链转移聚合(RAFT),制备了一种临界相转变温度(LCST)为42.5℃的温敏性两亲性嵌段共聚物PLA29-b-P(NIPAM29-co-DMAM13)。通过高温前驱体分解法制备了单分散超顺磁性纳米粒子Mn_(0.6)Zn_(0.4)Fe_2O_4;并采用自组装得到了载有药物(喜树碱,CPT)和磁性纳米粒子的磁热温敏复合载药胶束。通过透射电子显微镜、紫外光分光光度计以及MTT等对该胶束的形态、药物控释能力和细胞毒性进行了研究。结果表明,该胶束具有良好的生物学和药物控释性能。同时,通过激光共聚焦显微镜与流式细胞仪研究了磁热温敏复合载药胶束在不同条件下对特定肿瘤细胞的生长抑制作用。结果表明,磁热疗和化疗的高效协同效应可促进肿瘤细胞对药物的吞噬,增强药物对肿瘤细胞的毒性。对该载药胶束的磁热化疗协同增效机制也进行了初步探究。

Synthesis of Magnetothermally Responsive Drug-loaded Micelles and its Enhanced Synergism of Thermo-chemotherapy to Tumor Cells

The thermosensitive block copolymer PLA29-b-P(NIPAM29-co-DMAM13) with a lower critical solution temperature (LCST) of 42.5 °C was synthesized by NIPAM and DMAM. By self-assembly, camptothecin CPT and magnetic nanoparticles Mn0.6Zn0.4Fe2O4 were encapsulated into block polymer to form the magnetothermally responsive drug-loaded micelles. The biological property and efficacy of the micelles were investigated and results showed that magnetocaloric effect can lead to a rapid release of drug from multi-functional drug-loaded micelles. The anti-tumor efficiency of multi-functional drug-loaded micelles in vitro can be improved significantly by magnetic thermochemotherapy. The synergistic mechanisms of thermo-chemotherapy were further studied as well.